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TGF-beta1 regulates the inflammatory response during chronic neurodegeneration

TGF-beta1 regulates the inflammatory response during chronic neurodegeneration
TGF-beta1 regulates the inflammatory response during chronic neurodegeneration
The ME7 model of murine prion disease shows an atypical inflammatory response characterized by morphologically activated microglia and an anti-inflammatory cytokine profile with a marked expression of TGF?1. The investigation of the role of TGF?1 during a time course disease shows that its expression is correlated with (i) the onset of behavioral abnormalities, (ii) increased activated microglia, (iii) thickening of the basement membrane, and (iv) is associated with increased PrPsc deposition. Increasing TGF?1 using an adenoviral vector has no significant impact on prion-associated behavioral impairments or on neuropathology. In contrast, inhibition of TGF?1 activity using an adenovirus expressing decorin induces severe cerebral inflammation, expression of inducible nitric oxide synthase and acute neuronal death in prion-diseased animals only. These data suggest that TGF?1 plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage
inflammation, nitric-oxide, transforming growth-factor-beta-1, model, impact, neuropathology, disease, smooth-muscle-cells, neurodegeneration, central-nervous-system, growth-factor-beta, creutzfeldt-jakob-disease, tgf-beta, inos, murine prion disease, chronic neurodegeneration, activation, alzheimers-disease, decorin, tgf?1, mediated gene-transfer, abnormalities, priori, microglia
0969-9961
638-650
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Docagne, F.
5997c6a4-db39-4216-b41b-e0bcf29b6cf2
Scott, H.
68f5d547-0d51-4747-bb8e-760e2cf3d545
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Boche, D.
bdcca10e-6302-4dd0-919f-67218f7e0d61
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Docagne, F.
5997c6a4-db39-4216-b41b-e0bcf29b6cf2
Scott, H.
68f5d547-0d51-4747-bb8e-760e2cf3d545
Perry, VH.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Boche, D., Cunningham, C., Docagne, F., Scott, H. and Perry, VH. (2006) TGF-beta1 regulates the inflammatory response during chronic neurodegeneration. Neurobiology of Disease, 22 (3), 638-650. (doi:10.1016/j.nbd.2006.01.004).

Record type: Article

Abstract

The ME7 model of murine prion disease shows an atypical inflammatory response characterized by morphologically activated microglia and an anti-inflammatory cytokine profile with a marked expression of TGF?1. The investigation of the role of TGF?1 during a time course disease shows that its expression is correlated with (i) the onset of behavioral abnormalities, (ii) increased activated microglia, (iii) thickening of the basement membrane, and (iv) is associated with increased PrPsc deposition. Increasing TGF?1 using an adenoviral vector has no significant impact on prion-associated behavioral impairments or on neuropathology. In contrast, inhibition of TGF?1 activity using an adenovirus expressing decorin induces severe cerebral inflammation, expression of inducible nitric oxide synthase and acute neuronal death in prion-diseased animals only. These data suggest that TGF?1 plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage

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More information

Published date: June 2006
Keywords: inflammation, nitric-oxide, transforming growth-factor-beta-1, model, impact, neuropathology, disease, smooth-muscle-cells, neurodegeneration, central-nervous-system, growth-factor-beta, creutzfeldt-jakob-disease, tgf-beta, inos, murine prion disease, chronic neurodegeneration, activation, alzheimers-disease, decorin, tgf?1, mediated gene-transfer, abnormalities, priori, microglia

Identifiers

Local EPrints ID: 40591
URI: http://eprints.soton.ac.uk/id/eprint/40591
ISSN: 0969-9961
PURE UUID: 11f80366-8835-498c-8f16-e968263bdcd3
ORCID for D. Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 07 Jul 2006
Last modified: 17 Dec 2019 01:52

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Contributors

Author: D. Boche ORCID iD
Author: C. Cunningham
Author: F. Docagne
Author: H. Scott
Author: VH. Perry

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